This invention relates to new and useful anti-inflammatory compositions for topical administration containing as an active ingredient, piroxicam, viz., N-(2-pyridyl)-2-methyl-4-hydroxy-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide, which is a compound of the formula: ##STR1## More particularly, this invention relates to certain novel anti-inflammatory pharmaceutical compositions for external use comprising an effective anti-inflammatory amount of piroxicam, nontoxic bases for topical formulation and appropriate solvents therefor.
Piroxicam is a nonsteroidal anti-inflammatory agent described and claimed under its chemical name by J. G. Lombardino in U.S. Pat. No. 3,591,584 and it is highly effective in therapy when administered to mammalian subjects suffering from chronic arthritic rheumatism, arthritis deformans, low back pain, shoulder pain, cerrico-omo-brachial syndrome, trauma or the pain caused by tooth extraction. Piroxicam is sold in capsule form world-wide and it is recognized to be a potent long-acting drug that ensures an effective piroxicam blood level when admininstered orally once a day.
Some of the above diseases require a relatively long period of treatment in order to avoid or minimize side effects, and it would be desirable that the oral administration be replaced by the topical administration as the disease reaches a recuperative stage. Furthermore, the topical administration is suitable for a mild case or a case where the lesion is localized.
This invention is meant to provide anti-inflammatory compositions suitable for topical administration: these compositions are characterized in that they comprise an effective anti-inflammatory amount of piroxicam, nontoxic bases for topical formulation and solvents.
Piroxicam is very active as an anti-inflammatory agent, but it is sparingly soluble in water and is not liposoluble. When piroxicam is simply compounded in suspension with conventional bases for ointment or cream, it is poorly absorbed through skin and does not afford expected therapeutical effects. Additionally, the formulation so produced is very sticky and unpleasant to apply to a wide area of the skin. The active ingredients in the formulation may also be lost easily when in contact with clothing. In this connection, it seems possible to apply piroxicam in the form of a tincture after dissolving same in an alcoholic solvent such as ethanol. However, piroxicam will precipitate on the skin due to the evaporation of the solvent and will not be absorbed through the skin.
A gel ointment is prepared by adding a polymer to a lower alkanol-water system. It is generally a preferred form for topical administration because it is refreshing and not sticky. Unfortunately, the gel ointment cannot be formulated with piroxicam according to the standard techniques since piroxicam is sparingly soluble in water or any other solvent. Piroxicam, in the presence of moisture, turns into a hydrate thereof which is less soluble than piroxicam itself and this hydrate crystallizes out gradually. This not only reduces the absorbability of piroxicam through skin, but also impairs the coating and stability of the gel ointment.
A further problem arises when the gel ointment is applied to the skin in that dermal salt causes crystallization of piroxicam. This hydrate forms a yellow deposit on the skin. The hydrate will also come off when in contact with clothing or other material.
A similar problem arises when the gel ointment is applied directly to sweating skin, viz., a polymer gel-forming agent in the ointment is salted out and, as a result, the ointment agglomerates on the skin instead of forming a film layer. This affords unpleasantness to the user and the active ingredient is lost, whereby poor therapeutic effects are obtained.